Welcome to the Pediatric Obesity Column for Journal of Pediatric Surgical Nursing! This column's mission is to provide information and resources to the pediatric surgical nurse caring for children affected by obesity. Our goal is to share emerging information and strategies based on physiology and biochemistry that can be incorporated into the practitioner's daily practice.

In the last quarter's column, we shared some basic concepts of three of the body's many energy regulating systems: hunger, hedonic, and stress. In this edition, we touch broadly on effects to the body when these systems are damaged or altered. How this damage occurs continues to be studied. When intricacies of body energy regulation are better understood, more effective treatment can be further developed.

To review, the hypothalamus controls the body's master energy plan by identifying, interpreting, and directing energy intake, metabolism, and storage. Hormones such as leptin, insulin, and cortisol; the sympathetic and parasympathetic nervous systems; and central nervous system structures such as the hypothalamus, ventromedial hypothalamus, ventral tegmental area, nucleus accumbens, and amygdala all play a role in energy management. Disease, injury, or alteration of any of these structures/hormones (and many others not mentioned here) will alter energy balance. Obesity is one of the consequences of this energy imbalance (Guyenet & Schwartz, 2012).

The body can be divided into two energy areas: lean body mass (organs such as the heart, brain, liver, kidney, muscle, etc.) and adipose cells. Organs burn energy; adipose cells store energy. Redundant and synergistic systems provide ongoing feedback to the brain and peripheral organs to either increase caloric intake and decrease energy expenditure (orexogenic) or decrease caloric intake and increase caloric expenditure (anorexogenic; Lustig, 2012).

In physics, the "calories in equals calories out" equation works well. In physiology, it appears to be more complex. The body is designed to maintain homeostasis and does so with great precision. Examples include maintaining consistent heart rate, blood pressure, sodium, and glucose. No matter how much water an individual ingests (unless one has diabetes insipidus), the kidneys will regulate urine output to maintain a normal sodium level. The same is true of insulin and leptin. Calorie ingestion causes insulin levels to increase, leptin levels to decrease, and glucose to be processed, resulting in insulin and leptin levels returning to normal. Glucose levels return to normal through either organ energy burning or adipose storage; thus, the body strives to maintain its normal weight or set point.

Over time and usage, the body's energy regulatory system efficiency may decrease. Using the example of calorie ingestion, the response may be inefficient processing of glucose (higher glucose levels), increased circulating insulin, increased leptin, and higher adipose storage, leading to a higher weight set point. Increased leptin levels are a maladaptive response also termed leptin resistance. As with the similar maladaptive response of increased insulin levels (insulin resistance), both leptin and insulin continue to be produced, despite rising levels. This is in response to the hypothalamus' inability to recognize the higher levels, thus falsely interpreting that these levels are low and that more needs to be produced. The body responds by ingesting more calories because high insulin levels need glucose to process and the high leptin level is misinterpreted as a low leptin level (starvation), requiring more calories. Physiologically, elevated leptin is blocked from its receptor in the hypothalamus by high levels of insulin, triggering further ingestion of calories as the brain tells the body that it is starving because it is unable to read the leptin message from adipose tissue (Schneeberger, Gomis, & Claret, 2014).

In regard to the three energy regulating pathways discussed here, chronically elevated insulin levels can lead to obesity and metabolic syndrome (MS). In the hunger pathway, chronically elevated insulin levels at the ventromedial hypothalamus inhibit leptin signaling (starvation) and increase vagal activity (hunger). In the hedonic pathway, chronically elevated insulin levels inhibit leptin, decreasing satiety. Chronic activation of the amygdala increases stress (cortisol levels), also chronically increasing insulin and resulting in a cascade of results similar to those in the hedonic pathway (Schneeberger et al., 2014). Unless intervention occurs, the energy regulating systems and organs become overwhelmed, indicating MS. MS typically includes prediabetes (elevated fasting glucose or hemoglobin A1c) or diabetes, hypertension, fatty liver disease, increased waist circumference, and dyslipidemia.

The inability of the hypothalamus to interpret leptin and insulin levels correctly is believed to be a problem at the receptor level in neurons of the hypothalamus and its substructures. In an exciting area of research, these receptors are being mapped. From this knowledge of structure and function, therapies will be devised for specific receptor deficiencies. As with other complex physiological problems (e.g., cancer), more specific understanding of where the system fails allows for tailored therapy. As we learn more about the physiology of obesity and the complexity and redundancy that protect the set point, we will increase our understanding of why certain interventions benefit one patient but not another (Ochner, Tsai, Kushner, & Wadden, 2015; Schneeberger et al., 2014).

This column touches on only three of many potential systems that regulate the body's energy management systems. Under study are other hormones (e.g., adipokines, gastrointestinal peptides), central nervous system structures, environmental modulators (e.g., circadian rhythm, thermoregulation, brown fat, microbiota, infection), and genes and epigenetics that orchestrate our species' complex energy management systems (Schneeberger et al., 2014). In the most basic sense, physiology drives behavior. Obesity is not a behavioral disease. We need to see behavioral interventions as augmentations to physiologically driven treatment, not as the primary therapy. As educated humans, we have the ability to understand and, in many areas, overcome physiology by using our knowledge to develop targeted treatment and influence our environment. Therapies that support understanding our physiology may be our best strategy to prevent and treat obesity.

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